These studies aim toward a more precise description of the complex interrelationships of glucose and insulin in man and an understanding of the nature of changes occurring in this regulatory system in states of altered carbohydrate metabolism (e.g., age, obesity, diabetes mellitus, uremia). The focus of current studies is the control which insulin exerts on glucose production and utilization in states of normal and altered carbohydrate metabolism. The modeling effort is also directed toward a description of the role which glucose plays in insulin secretion in these same normal and abnormal states.